Airway tissue engineering: an update

Fishman, Jonathan; Wiles, Katherine; Lowdell, Mark W.; Coppi, Paolo De; Elliott, Martin J.; Atala, Anthony; Birchall, Martin A.

doi:10.1517/14712598.2014.938631

Cited by 70 publications

(66 citation statements)

References 98 publications

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“…The first bioengineered tracheal transplantation took place in 2008 and more have followed (3)(4)(5), making upper airway reconstruction among the first in the field to see clinical translation of advanced tissue-engineering methods (6). Although the clinical need for these transplants is established, many aspects of this nascent therapy remain to be investigated in detail (7), including the use of decellularized versus synthetic scaffolds (8), the value of graft prevascularization or enhanced angiogenesis (9), and the optimal combination of growth factors and cultured cells to stimulate regeneration (10,11).…”

mentioning

confidence: 99%

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering

Butler

Hynds

Gowers

et al. 2016

Am J Respir Crit Care Med

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179

210

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Rationale: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts.Objectives: To define a scalable cell culture system to deliver airway epithelium to clinical grafts.Methods: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T31Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation-dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures.

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mentioning

confidence: 99%

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering

Butler

Hynds

Gowers

et al. 2016

Am J Respir Crit Care Med

Self Cite

179

210

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“…Despite these successes, a number of challenges remain. Mechanical properties of tissues and organs may be affected by the decellularization process, the process may remove various types and amounts of ECMassociated signaling molecules, and the processed tissue may degrade over time after transplantation without commensurate replacement by host cells (34,35). The detergents and procedures used to strip cells and other immunogenic components from donor organs and techniques to recellularize stripped tissue before implantation are actively being optimized.…”

Section: Therapies At the Preclinical Stage And In Clinical Testingmentioning

confidence: 99%

Regenerative medicine: Current therapies and future directions

Mao

Mooney

2015

Proc. Natl. Acad. Sci. U.S.A.

707

439

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Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.regenerative medicine | tissue engineering | biomaterials | review

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“…Combination of natural and synthetic scaffolds with the desired cell types in one process further improves the efficiency of production. This approach has been remarkably successful for more uniform and structural tissues such as bone and trachea (Fedorovich et al 2010;Fishman et al 2014). Attempts at creating more complex organ structures such as kidney or lung have proven more challenging, requiring accurate interactions between divergent cell types for function.…”

Section: Organ Printingmentioning

confidence: 99%

Synthetic Biology in Cell and Organ Transplantation

Stevens

2016

Cold Spring Harb Perspect Biol

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The transplantation of cells and organs has an extensive history, with blood transfusion and skin grafts described as some of the earliest medical interventions. The speed and efficiency of the human immune system evolved to rapidly recognize and remove pathogens; the human immune system also serves as a barrier against the transplant of cells and organs from even highly related donors. Although this shows the remarkable effectiveness of the immune system, the engineering of cells and organs that will survive in a host patient over the long term remains a steep challenge. Progress in the understanding of host immune responses to donor cells and organs, combined with the rapid advancement in synthetic biology applications, allows the rational engineering of more effective solutions for transplantation.

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Airway tissue engineering: an update

Cited by 70 publications

References 98 publications

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering

Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering

Regenerative medicine: Current therapies and future directions

Synthetic Biology in Cell and Organ Transplantation

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